Scoring systems for prediction of malaria and dengue fever in non-endemic areas among travellers arriving from tropical and subtropical areas.

BACKGROUND: Fever is a common symptom among travellers returning from tropical/subtropical areas to Europe, and promptly distinguishing severe illnesses from self-limiting febrile syndromes is important but can be challenging due to non-specific clinical presentation. METHODS: A cross-sectional study enrolled adults and children who sought care during 2015-2020 at Karolinska University Hospital, Stockholm, Sweden with fever within 2 months after returning from travel to a tropical/subtropical area. Data on symptoms and laboratory parameters were prospectively and retrospectively collected. Two separate scoring systems for malaria and dengue were developed based on backward elimination regressions. RESULTS: In total, 2113 adults (18-94 years) and 202 children (1-17 years) were included, with 112 (4.8%) confirmed malaria by blood thick smear and 90 (3.9%) PCR/serology dengue-positive cases. Malaria was more likely in a patient who had visited sub-Saharan Africa and presented with combination of thrombocytopenia, anaemia and fever ≥39.5°C. Leucopenia, muscle pain and rash after travelling to Asia or South/Latin America indicated high probability of dengue. Two scoring systems with points between 0 and 7 for prediction of malaria or dengue were created based on the above predictors. Scores ≥3 indicated >80% sensitivity and specificity for malaria and >90% specificity for dengue in children and adults (area under the curve (AUC) for dengue: 0.92 in adults (95% CI 0.90 to 0.95) and 0.95 in children (95% CI 0.88 to 1.0); AUC for malaria: 0.93 in adults (95% CI 0.91 to 0.96) and 0.88 in children (95% CI 0.78 to 0.99)). Internal validation of optimism and overfitting was managed with bootstrap. CONCLUSION: The presented scoring systems provide novel tools for structured assessment of patients with tropical fever in a non-endemic area and highlight clinical signs associated with a potential severe aetiology to direct the need for microbial investigation.

Under-five mortality in the Democratic Republic of the Congo: secondary analyses of survey and conflict data by province.

Objective: To compare coverage of key child health policy indicators across provinces and to explore their association with under-five mortality and level of conflict in the Democratic Republic of the Congo. Methods: We made a secondary analysis of nationally representative data from 1380 health facilities and 20 792 households in 2017-2018. We analysed provincial-level data on coverage of 23 different indicators for improving common causes of childhood mortality, combined into mean scores for: newborn health, pneumonia, diarrhoea, malaria and safe environment. Using negative binomial regression we compared the scores with provincial-level under-five mortality. With binary logistic regression at the individual level we compared indicators (outcome) with living in a conflict-affected province (exposure). Findings: All grouped coverage scores demonstrated large ranges across the 26 provinces: newborn health: 20% to 61%; pneumonia: 26% to 86%; diarrhoea: 25% to 63%; malaria: 22% to 53%; and safe environment: 4% to 53%. The diarrhoea score demonstrated the strongest association with under-five mortality (adjusted coefficient: -0.026; 95% confidence interval: -0.045 to -0.007). Conflict-affected provinces had both the highest as well as the lowest mortality rates and indicator coverages. The odds of coverage were higher in conflict-affected provinces for 13 out of 23 indicators, whereas in provinces unaffected by conflict only one indicator had higher odds of coverage. Conclusion: Conflict alone is a poor predictor for child health. Ensuring that children in unaffected provinces are not neglected while addressing the needs of the most vulnerable in conflict settings is important. Prevent, protect and treat strategies for diarrhoeal disease could help improve equity in child survival.

Prospective cohort study of referred Malawian children and their survival by hypoxaemia and hypoglycaemia status.

Objective: To investigate survival in children referred from primary care in Malawi, with a focus on hypoglycaemia and hypoxaemia progression. Methods: The study involved a prospective cohort of children aged 12 years or under referred from primary health-care facilities in Mchinji district, Malawi in 2019 and 2020. Peripheral blood oxygen saturation (SpO2) and blood glucose were measured at recruitment and on arrival at a subsequent health-care facility (i.e. four hospitals and 14 primary health-care facilities). Children were followed up 2 weeks after discharge or their last clinical visit. The primary study outcome was the case fatality ratio at 2 weeks. Associations between SpO2 and blood glucose levels and death were evaluated using Cox proportional hazards models and the treatment effect of hospitalization was assessed using propensity score matching. Findings: Of 826 children recruited, 784 (94.9%) completed follow-up. At presentation, hypoxaemia was moderate (SpO2: 90-93%) in 13.1% (108/826) and severe (SpO2: < 90%) in 8.6% (71/826) and hypoglycaemia was moderate (blood glucose: 2.5-4.0 mmol/L) in 9.0% (74/826) and severe (blood glucose: < 2.5 mmol/L) in 2.3% (19/826). The case fatality ratio was 3.7% (29/784) overall but 26.3% (5/19) in severely hypoglycaemic children and 12.7% (9/71) in severely hypoxaemic children. Neither moderate hypoglycaemia nor moderate hypoxaemia was associated with mortality. Conclusion: Presumptive pre-referral glucose treatment and better management of hypoglycaemia could reduce the high case fatality ratio observed in children with severe hypoglycaemia. The morbidity and mortality burden of severe hypoxaemia was high; ways of improving hypoxaemia identification and management are needed.

Health facility readiness to care for high risk newborn babies for early childhood development in eastern Uganda.

BACKGROUND: The neonatal mortality rate in Uganda has barely changed over the past decades, estimated at 28/1000 and 27/1000 live births in 2006 and 2016 respectively. The survivors have a higher risk of developing neurodevelopmental disabilities (NDD) due to brain insults from perinatal complications related to poor quality of health services during pregnancy, around the time of birth, and during the postnatal period. This study aimed to assess health facility readiness to care for high risk newborn babies in order to inform programming that fosters early childhood development in eastern Uganda. METHODS: A cross sectional study of 6 hospitals and 10 higher level health centers that offer comprehensive maternal and newborn care was carried out in February 2020 in eastern Uganda. A World Health Organization Service Availability and Readiness Assessment tool (SARA) was adapted and used to assess the health facility readiness to manage maternal and neonatal conditions that are related to NDD. In addition, 201 mothers of high risk newborn babies were interviewed on their satisfaction with health services received. Readiness scores were derived from percentage average facilities with available infrastructure and essential medical commodities to manage neonatal complications. Descriptive statistics were computed for client satisfaction with service provision, and p values used to compare private not for profit to public health facilities. RESULTS: There was limited availability in numbers and skilled human resource especially the neonatal nurses. Hospitals and health centers scored least in preterm and hypothermia care, with averages of 38% and 18% respectively. The highest scores were in essential newborn care, with readiness of 78% and 85% for hospitals and health centers, followed by resuscitation at 78% and 77%, respectively. There were no guidelines on positive interaction with newborn babies to foster neurodevelopment. The main cause of admission to neonatal care units was birth asphyxia followed by prematurity, indicative of intrapartum care challenges. The overall client satisfaction with health services was higher in private not for profit facilities at 91% compared to public hospitals at 73%, p = 0.017. CONCLUSION: Health facility readiness was inadequate in management of preterm complications. Efforts should, therefore, be geared to improving availability of inputs and quality of emergency obstetric and newborn care in order to manage high risk newborns and reduce the burden of NDD in this setting.

Accessibility of basic paediatric emergency care in Malawi: analysis of a national facility census.

BACKGROUND: Emergency care is among the weakest parts of health systems in low-income countries with both quality and accessibility constraints. Previous studies estimated accessibility to surgical or emergency care based on population travel times to nearest hospital with no assessment of hospital readiness to provide such care. We analysed a Malawi national facility census with comprehensive inventory audits and geocoded facility locations to identify hospitals equipped to provide basic paediatric emergency care with estimated travel times to these hospitals from non-equipped facilities and in relation to Malawi's population distribution. METHODS: We analysed a Malawi national facility census in 2013-2014 to identify hospitals equipped to manage critically ill children according to an extended version of WHO Emergency Triage, Assessment and Treatment (ETAT) guidelines. These guidelines include 25 components including staff, transport, equipment, diagnostics, medications, fluids, feeds and consumables that defined an emergency-equipped hospital in our study. We estimated travel times to emergency-equipped hospitals from non-equipped facilities and relative to population distributions using geocoded facility locations and an established accessibility mapping approach using global road network datasets from OpenStreetMap and Google. RESULTS: Four (3.5, 95% CI: 1.3-8.9) of 116 Malawi hospitals were emergency-equipped. Least available items were nasogastric tubes in 34.5% of hospitals (95% CI: 26.4-43.6), blood typing services (40.4, 95% CI: 31.9-49.6), micro nebulizers (50.9, 95% CI: 41.9-60.0), and radiology (54.2, 95% CI: 45.1-63.0). Nationally, the median travel time from non-equipped facilities to the nearest emergency-equipped hospital was 73 min (95% CI: 67-77) ranging 1-507 min. Approximately one-quarter (27%) of Malawians lived over 120 min from an emergency-equipped hospital with significantly better accessibility in Central than North and South regions (16% vs. 38 and 35%, p < 0.001). CONCLUSIONS: There are unacceptable deficiencies in accessibility of basic paediatric emergency care in Malawi. Reliable supply chains for essential drugs and commodities are needed, particularly nasogastric tubes, asthma drugs and blood, along with improved capacity for time-sensitive referral. Further child mortality reductions will require substantial investments to expand basic paediatric emergency care into all Malawi hospitals for better managing critically ill children at highest mortality risk.

Feeding practices and association of fasting and low or hypo glycaemia in severe paediatric illnesses in Malawi - a mixed method study.

BACKGROUND: The presence of low or hypo glycaemia in children upon admission to hospital in low income countries is a marker for poor outcome. Fasting during illness may contribute to low blood glucose and caretakers' feeding practices during childhood illnesses may thus play a role in the development of low or hypo glycaemia. This study aims to describe the caretaker's feeding practices and association of fasting with low or hypo glycaemia in sick children in Malawi. METHODS: A mixed method approach was used combining quantitative cross-sectional data for children aged 0-17 years admitted to Queen Elizabeth Central Hospital (QECH), a tertiary hospital in Malawi, with qualitative focus group discussions conducted with caretakers of young children who were previously referred to QECH from the five health centres around QECH. Logistic regression was used to analyse the quantitative data and thematic content analysis was conducted for qualitative data analysis. RESULTS: Data for 5131 children who were admitted through the hospital's Paediatric Accident and Emergency Department (A&E) were analysed whereof 2.1% presented with hypoglycaemia (< 2.5 mmol/l) and 6.6% with low glycaemia (≥2.5mmoll/l - < 5 mmol/l). Fasting for more than eight hours was associated with low glycaemia as well as hypoglycaemia with Adjusted Odds Ratios (AOR) of 2.9 (95% Confidence Interval (CI) of 2.3-3.7) and 4.6, (95% CI 3.0-7.0), respectively. Caretakers demonstrated awareness of the importance of feeding during childhood illness and reported intensified feeding attention to sick children but face feeding challenges when illness becomes severe causing them to seek care at a health facility. CONCLUSION: Results suggests that caretakers understand the importance of feeding during illness and make efforts to intensify feeding a sick child but challenges occur when illness is severe leading to fasting. Fasting among children admitted to hospitals may serve as a marker of severe illness and determine those at risk of low and hypoglycaemia.

Prevalence and associated factors of neurodevelopmental disability among infants in eastern Uganda: a population based study.

BACKGROUND: Neurodevelopmental disability (NDD) is increasingly acknowledged as one of the important causes of disease burden in low income countries. None the less, there is a dearth of data on the burden of NDD and its determinants in these settings. We aimed to establish the prevalence and factors associated with NDD among infants in Eastern Uganda. METHODS: We assessed 487 infants aged 9-12 months within Iganga-Mayuge Health Demographic Surveillance Site in Eastern Uganda using the Malawi Developmental Assessment Tool. The tool has four domains: gross motor, fine motor, language and social domains. An infant failed a domain if she/he failed more than two parameters of the expected at his/her age. We interviewed mothers on factors that could influence the infants' neurodevelopmental outcomes. Data were analysed using STATA version 14. We used odds ratios and 95% confidence intervals to assess statistical significance of associations. RESULTS: Of the 487 infants, 62(12.7%) had an NDD in at least one of the domains. The most affected was social behaviour where 52(10.7%) infants had an NDD. Severe impairment was seen among 9(1.8%) infants with NDD in either three or four domains. Factors associated with NDD at multivariate logistic regression included: parity of more than three children (aOR = 1.8, 95% CI: 1.02-3.18); failure to cry at birth (aOR = 3.6, 95% CI: 1.46-9.17) and post-neonatal complications (aOR = 4.15, 95% CI: 1.22-14.10). Low birth weight, immediate and exclusive breast feeding were not significantly associated with NDD. CONCLUSION: We found a high NDD burden among infants particularly in the social behaviour domain. To optimise the socio-neural development of infants, programs are needed to educate and work with families on how to engage and stimulate infants. Existing immunisation clinics and community health worker strategies provide an excellent opportunity for stemming this burden.

Point-of-care assessment of C-reactive protein and white blood cell count to identify bacterial aetiologies in malaria-negative paediatric fevers in Tanzania.

OBJECTIVE: To assess the role of point-of-care (PoC) assessment of C-reactive protein (CRP) and white blood cell (WBC) count to identify bacterial illness in Tanzanian children with non-severe non-malarial fever. METHODS: From the outpatient department of a district hospital in Tanzania, 428 patients between 3 months and 5 years of age who presented with fever and a negative malaria test were enrolled. All had a physical examination and bacterial cultures from blood and urine. Haemoglobin, CRP and WBC were measured by PoC devices. RESULTS: Positive blood cultures were detected in 6/428 (1.4%) children and urine cultures were positive in 24/401 (6.0%). Mean WBC was similar in children with or without bacterial illness (14.0 × 109 , 95% CI 12.0-16.0 × 109 vs. 12.0 × 109 , 95% CI 11.4-12.7 × 109), while mean CRP was higher in children with bacterial illness (41.0 mg/l, 95% CI 28.3-53.6 vs. 23.8 mg/l, 95% CI 17.8-27.8). In ROC analysis, the optimum cut-off value for CRP to identify bacterial illness was 19 mg/l but with an area under the curve of only 0.62. Negative predictive values exceeded 80%, while positive predictive values were under 40%. CONCLUSION: WBC and CRP levels had limited value in identifying children with bacterial infections. The positive predictive values for both tests were too low to be used as single tools for treatment decisions.

Variability of respiratory rate measurements in children suspected with non-severe pneumonia in north-east Tanzania.

OBJECTIVE: Measurement of respiratory rate is an important clinical sign in the diagnosis of pneumonia but suffers from interobserver variation. Here, we assess the use of video recordings as a quality assurance tool that could be useful both in research and in training of staff. METHODS: Respiratory rates (RR) were recorded in children aged 2-59 months presenting with cough or difficulty breathing at two busy outpatient clinics in Tanzania. Measurements were repeated at 10-min intervals in a quiet environment with simultaneous video recordings that were independently reviewed by two paediatricians. RESULTS: Eight hundred and fifty-nine videos were sent to two paediatricians; 148 (17.2%) were considered unreadable by one or both. For the 711 (82.8%) videos that were readable by both paediatricians, there was perfect agreement for the presence of raised RR with a kappa value (κ) of 0.85 (P < 0.001); and in 476 (66.9%) cases, both paediatricians agreed on the RR within 2 breaths per minute (±2 bpm). A reported illness of 5 days or more was associated with unreadable video recordings (OR = 3.44, CI: 1.5-6.08; P < 0.001). The multilevel model showed that differences between observers accounted for only 13% of the variability in RR. CONCLUSION: Video recordings are reliable tools for quality assurance of RR measurements in children with suspected pneumonia. Videos with a clear view of respiratory movements may also be useful in training primary healthcare staff.

"It is good to take her early to the doctor" - mothers' understanding of childhood pneumonia symptoms and health care seeking in Kilimanjaro region, Tanzania.

BACKGROUND: Pneumonia is among the leading causes of avoidable deaths for young children globally. The main burden of mortality falls on children from poor and rural families who are less likely to obtain the treatment they need, highlighting inequities in access to effective care and treatment. Caretakers' illness perceptions and care-seeking practices are of major importance for children with pneumonia to receive adequate care. This study qualitatively explores the caretaker concepts of childhood pneumonia in relation to treatment seeking behaviour and health worker management in Moshi urban district, Tanzania. METHODS: In May - July 2013 data was gathered through different qualitative data collection techniques including five focus group discussions (FGDs) with mothers of children under-five years of age. The FGDs involved free listing of pneumonia symptoms and video presentations of children with respiratory symptoms done, these were triangulated with ten case narratives with mothers of children admitted with pneumonia and eleven in-depth interviews with hospital health workers. Transcripts were coded and analysed using qualitative content analysis. RESULTS: Mothers demonstrated good awareness of common childhood illnesses including pneumonia, which was often associated with symptoms such as cough, flu, chest tightness, fever, and difficulty in breathing. Mothers had mixed views on causative factors and treatments options but generally preferred modern medicine for persisting and severe symptoms. However, all respondent reported access to health facilities as a barrier to care, associated with transport, personal safety and economic constraints. CONCLUSION: Local illness concepts and traditional treatment options did not constitute barriers to care for pneumonia symptoms. Poor access to health facilities was the main barrier. Decentralisation of care through community health workers may improve access to care but needs to be combined with strengthened referral systems and accessible hospital care for those in need.

Causes of non-malarial febrile illness in outpatients in Tanzania.

OBJECTIVE: In sub-Saharan Africa, the use of malaria rapid diagnostic tests (mRDT) has raised awareness of alternative fever causes in children but few studies have included adults. To address this gap, we conducted a study of mRDT-negative fever aetiologies among children and adults in Tanzania. METHODS: A total of 1028 patients aged 3 months to 50 years with a febrile illness and negative mRDT were enrolled from a Tanzanian hospital outpatient department. All had a physical examination and cultures from blood, nasopharynx/throat and urine. Patients were followed on Days 7 and 14 and children meeting WHO criteria for pneumonia were followed on Day 2 with chest radiology. RESULTS: Respiratory symptoms were the most frequent presenting complaint, reported by 20.3% of adults and 64.0% (339/530) of children. Of 38 X-rayed children meeting WHO pneumonia criteria, 47.4% had a normal X-ray. Overall, only 1.3% of 1028 blood cultures were positive. Salmonella typhi was the most prevalent pathogen isolated (7/13, 53.8%) and S. typhi patients reported fever for a median of 7 days (range 2-14). Children with bacteraemia did not present with WHO symptoms requiring antibiotic treatment. Young children and adults had similar prevalences of positive urine cultures (24/428 and 29/498, respectively). CONCLUSION: Few outpatient fevers are caused by blood stream bacterial infection, and most adult bacteraemia would be identified by current clinical guidelines although paediatric bacteraemia may be more difficult to diagnose. While pneumonia may be overdiagnosed, urinary tract infection was relatively common. Our results emphasise the difficulty in identifying African children in need of antibiotics among the majority who do not.

It could be viral but you don't know, you have not diagnosed it: health worker challenges in managing non-malaria paediatric fevers in the low transmission area of Mbarara District, Uganda.

BACKGROUND: In 2012, Uganda initiated nationwide deployment of malaria rapid diagnostic tests (RDT) as recommended by national guidelines. Yet growing concerns about RDT non-compliance in various settings have spurred calls to deploy RDT as part of enhanced support packages. An understanding of how health workers currently manage non-malaria fevers, particularly for children, and challenges faced in this work should also inform efforts. METHODS: A qualitative study was conducted in the low transmission area of Mbarara District (Uganda). In-depth interviews with 20 health workers at lower level clinics focused on RDT perceptions, strategies to differentiate non-malaria paediatric fevers, influences on clinical decisions, desires for additional diagnostics, and any challenges in this work. Seven focus group discussions were conducted with caregivers of children under 5 years of age in facility catchment areas to elucidate their RDT perceptions, understandings of non-malaria paediatric fevers and treatment preferences. Data were extracted into meaning units to inform codes and themes in order to describe response patterns using a latent content analysis approach. RESULTS: Differential diagnosis strategies included studying fever patterns, taking histories, assessing symptoms, and analysing other factors such as a child's age or home environment. If no alternative cause was found, malaria treatment was reportedly often prescribed despite a negative result. Other reasons for malaria over-treatment stemmed from RDT perceptions, system constraints and provider-client interactions. RDT perceptions included mistrust driven largely by expectations of false negative results due to low parasite/antigen loads, previous anti-malarial treatment or test detection of only one species. System constraints included poor referral systems, working alone without opportunity to confer on difficult cases, and lacking skills and/or tools for differential diagnosis. Provider-client interactions included reported caregiver RDT mistrust, demand for certain drugs and desire to know the 'exact' disease cause if not malaria. Many health workers expressed uncertainty about how to manage non-malaria paediatric fevers, feared doing wrong and patient death, worried caregivers would lose trust, or felt unsatisfied without a clear diagnosis. CONCLUSIONS: Enhanced support is needed to improve RDT adoption at lower level clinics that focuses on empowering providers to successfully manage non-severe, non-malaria paediatric fevers without referral. This includes building trust in negative results, reinforcing integrated care initiatives (e.g., integrated management of childhood illness) and fostering communities of practice according to the diffusion of innovations theory.

Integrated paediatric fever management and antibiotic over-treatment in Malawi health facilities: data mining a national facility census.

BACKGROUND: There are growing concerns about irrational antibiotic prescription practices in the era of test-based malaria case management. This study assessed integrated paediatric fever management using malaria rapid diagnostic tests (RDT) and Integrated Management of Childhood Illness (IMCI) guidelines, including the relationship between RDT-negative results and antibiotic over-treatment in Malawi health facilities in 2013-2014. METHODS: A Malawi national facility census included 1981 observed sick children aged 2-59 months with fever complaints. Weighted frequencies were tabulated for other complaints, assessments and prescriptions for RDT-confirmed malaria, IMCI-classified non-severe pneumonia, and clinical diarrhoea. Classification trees using model-based recursive partitioning estimated the association between RDT results and antibiotic over-treatment and learned the influence of 38 other input variables at patient-, provider- and facility-levels. RESULTS: Among 1981 clients, 72 % were tested or referred for malaria diagnosis and 85 % with RDT-confirmed malaria were prescribed first-line anti-malarials. Twenty-eight percent with IMCI-pneumonia were not prescribed antibiotics (under-treatment) and 59 % 'without antibiotic need' were prescribed antibiotics (over-treatment). Few clients had respiratory rates counted to identify antibiotic need for IMCI-pneumonia (18 %). RDT-negative children had 16.8 (95 % CI 8.6-32.7) times higher antibiotic over-treatment odds compared to RDT-positive cases conditioned by cough or difficult breathing complaints. CONCLUSIONS: Integrated paediatric fever management was sub-optimal for completed assessments and antibiotic targeting despite common compliance to malaria treatment guidelines. RDT-negative results were strongly associated with antibiotic over-treatment conditioned by cough or difficult breathing complaints. A shift from malaria-focused 'test and treat' strategies toward 'IMCI with testing' is needed to improve quality fever care and rational use of both anti-malarials and antibiotics in line with recent global commitments to combat resistance.

Effect of context on respiratory rate measurement in identifying non-severe pneumonia in African children.

OBJECTIVE: Cough or difficult breathing and an increased respiratory rate for their age are the commonest indications for outpatient antibiotic treatment in African children. We aimed to determine whether respiratory rate was likely to be transiently raised by a number of contextual factors in a busy clinic leading to inaccurate diagnosis. METHODS: Respiratory rates were recorded in children aged 2-59 months presenting with cough or difficulty breathing to one of the two busy outpatient clinics and then repeated at 10-min intervals over 1 h in a quiet setting. RESULTS: One hundred and sixty-seven children were enrolled with a mean age of 7.1 (SD ± 2.9) months in infants and 27.6 (SD ± 12.8) months in children aged 12-59 months. The mean respiratory rate declined from 42.3 and 33.6 breaths per minute (bpm) in the clinic to 39.1 and 32.6 bpm after 10 min in a quiet room and to 39.2 and 30.7 bpm (P < 0.001) after 60 min in younger and older children, respectively. This resulted in 11/13 (85%) infants and 2/15 (13%) older children being misclassified with non-severe pneumonia. In a random effects linear regression model, the variability in respiratory rate within children (42%) was almost as much as the variability between children (58%). Changing the respiratory rates cut-offs to higher thresholds resulted in a small reduction in the proportion of non-severe pneumonia mis-classifications in infants. CONCLUSION: Noise and other contextual factors may cause a transient increase in respiratory rate and consequently misclassification of non-severe pneumonia. However, this effect is less pronounced in older children than infants. Respiratory rate is a difficult sign to measure as the variation is large between and within children. More studies of the accuracy and utility of respiratory rate as a proxy for non-severe pneumonia diagnosis in a busy clinic are needed.

Effect of diagnostic testing on medicines used by febrile children less than five years in 12 malaria-endemic African countries: a mixed-methods study.

BACKGROUND: In 2010, WHO revised guidelines to recommend testing all suspected malaria cases prior to treatment. Yet, evidence to assess programmes is largely derived from limited facility settings in a limited number of countries. National surveys from 12 sub-Saharan African countries were used to examine the effect of diagnostic testing on medicines used by febrile children under five years at the population level, including stratification by malaria risk, transmission season, source of care, symptoms, and age. METHODS: Data were compiled from 12 Demographic and Health Surveys in 2010-2012 that reported fever prevalence, diagnostic test and medicine use, and socio-economic covariates (n=16,323 febrile under-fives taken to care). Mixed-effects logistic regression models quantified the influence of diagnostic testing on three outcomes (artemisinin combination therapy (ACT), any anti-malarial or any antibiotic use) after adjusting for data clustering and confounding covariates. For each outcome, interactions between diagnostic testing and the following covariates were separately tested: malaria risk, season, source of care, symptoms, and age. A multiple case study design was used to understand varying results across selected countries and sub-national groups, which drew on programme documents, published research and expert consultations. A descriptive typology of plausible explanations for quantitative results was derived from a cross-case synthesis. RESULTS: Significant variability was found in the effect of diagnostic testing on ACT use across countries (e.g., Uganda OR: 0.84, 95% CI: 0.66-1.06; Mozambique OR: 3.54, 95% CI: 2.33-5.39). Four main themes emerged to explain results: available diagnostics and medicines; quality of care; care-seeking behaviour; and, malaria epidemiology. CONCLUSIONS: Significant country variation was found in the effect of diagnostic testing on paediatric fever treatment at the population level, and qualitative results suggest the impact of diagnostic scale-up on treatment practices may not be straightforward in routine conditions given contextual factors (e.g., access to care, treatment-seeking behaviour or supply stock-outs). Despite limitations, quantitative results could help identify countries (e.g., Mozambique) or issues (e.g., malaria risk) where facility-based research or programme attention may be warranted. The mixed-methods approach triangulates different evidence to potentially provide a standard framework to assess routine programmes across countries or over time to fill critical evidence gaps.